Methods for preparing a fermented ginseng concentrate or powder

ABSTRACT

The present invention relates to a method for preparing a fermented ginseng concentrate. The method first involves subjecting ginseng to an extraction with a solvent to obtain a ginseng extract. Next, pectinase and beta-galactosidase are added to the ginseng extract under conditions effective to ferment the ginseng extract. The fermented extract is then concentrated to produce a fermented ginseng concentrate. The method may further involve drying the fermented ginseng concentrate to obtain fermented ginseng powder. Combinations of the invention ginseng materials with other active and/or inactive materials are also disclosed.

RELATED APPLICATIONS

The present application is related to U.S. application Ser. No.12/466,093, filed May 14, 2009, the entire contents of which areincorporated herein by reference.

TECHNICAL FIELD

The present invention relates to methods for preparing a fermentedginseng concentrate or powder.

BACKGROUND OF THE INVENTION

Panax ginseng C. A. Meyer (Araliaceae), is one of the medicinal plantsthat have long been used for treating various diseases in Asiancountries, including China, Korea, and Japan. In particular,ginsenosides (ginseng saponin), the main active ingredient of Panaxginseng, are known to have various physiological activities, such asanti-aging activity, anti-inflammatory activity, antioxidant activitiesin the central nervous system, cardiovascular system, and the immunesystem (Wu et al., J. Immunol., 148:1519-25, 1992; Lee, Facts aboutGinseng, the Elixir of Life., Hollyn International. New Jersey, 1992;Huang, The Pharmacology of Chinese Herbs. CRC Press. Florida, 1999),anti-diabetic activity (Chang, Pharmacology and Application of ChineseMaterial Medica. Vol. 1, World Scientific. Singapore, 1986), andanti-tumor activity (Sato et al., Biol. Pharm. Bull. 17:635-9, 1994;Mochizuki et al., Biol. Pharm. Bull. 18:1197-1202, 1995).

Further, ginsenosides are metabolized by bacteria inside the humanintestine after intake, where their metabolites are known to havevarious physiological activities (Karikura et al., Chem. Pharm. Bull.,39:2357-61, 1991; Kanaoda et al., J. Tradit. Med. 11:241-5, 1994; Akaoet al., Biol. Pharm. Bull., 21:245-9, 1998). For example, Rb1, Rb2, andRc, which are protopanaxadiol-type ginsenosides, are metabolized byhuman intestinal bacteria into IH-901(20-O-β-D-glucopyranosyl-20(S)-protopandaxadiol) (Hasegawa et al.,Planta Medica 63:463-40, 1997; Tawab et al., Drug Metab. Dispos.,31:1065-71, 2003), while Re and Rg1, protopanaxatriol-type ginsenosides,are metabolized into ginsenoside Rh1 or ginsenoside F1 (Hasegawa et al.,Planta Medica 63:463-40, 1997; Tawab et al., Drug Metab. Dispos.,31:1065-71, 2003), where the metabolites IH-901, Rh1, and F1 exhibitvarious physiological activities.

Specifically, IH-901 is generally known for its anti-diabetic (Choi etal., J. Ginseng Res. 31(2): 79-85, 2007) and immune-enhancingactivities. Further, IH-901 is known to induce an anti-metastasis oranti-cancer effect by blocking tumor invasion or preventing chromosomalmutation and tumor formation (Wakabayashi et al., Oncol. Res., 9:411-7,1998; Lee et al., Cancer Lett., 144:39-43, 1999).

Several researchers have tried to produce genuine prosapogenin orsapogenin by using methods, such as chemical synthesis, subacidhydrolysis, and alkali digestion (Han et al., Planta Medica 44:146-9,1982; Chen et al., Chem. Pharm. Bull. 35:1653-5, 1987; Elyakov et al.,Synthesis of the Ginseng Glycosides and Their Analogs. Proc. 6th Int.Ginseng Symp. Seoul 74-83, 1993). However, the above methods are knownto cause various side reactions, such as epimerization, hydration, andhydroxylation.

Thus, a number of methods that convert ginsenosides under mildconditions by utilizing enzymes (Ko et al., Biosci. Biotechnol. Biochem.64:2739-43, 2000; Ko et al., Planta Med. 69:285-6, 2003) or intestinalbacteria (Hasegawa et al., Planta Medica 63:463-40, 1997; Bae et al., J.Microbial. Biotechnol. 13:9-14, 2003) have been studied. Specifically,methods for preparing IH-901 by hydrolyzing diol-type ginsenosides withnaringinase, as well as methods for preparing IH-901 by administratingthe diol-type ginsenosides orally to a rat and then having them digestedin the colon have been developed. However, the above preparation methodswere found to have certain drawbacks in that the production yield ofIH-901 is extremely low and various secondary metabolites are produced,making it difficult to obtain highly pure IH-901 (Karikura et al., Chem.Pharm. Bull. 38:2859, 1990).

More recently, other methods for preparing IH-901 by reacting a varietyof enzymes with ginsenosides (Korean Laid-open Patent Publication No.2003-94757; Korean Patent Nos. 418604 and 377546) have been studied, butthe amount of IH-901 produced using these methods was found to be toolow to have any significant effect. Further, the above methods involvecomplicated steps and are unsuitable for preparing a fermented ginsengconcentrate having a high content of IH-901.

The present invention is directed to overcoming these deficiencies inthe art.

SUMMARY OF THE INVENTION

The present invention relates to a method for preparing a fermentedginseng concentrate. The method first involves subjecting ginseng to anextraction with a solvent to obtain a ginseng extract. Next, pectinaseand beta-galactosidase are added to the ginseng extract under conditionseffective to ferment the ginseng extract. Then, the fermented ginsengextract is concentrated to produce a fermented ginseng concentrate.

The present invention also relates to a method for preparing a fermentedginseng concentrate. The method first involves suspending ginseng in afirst solvent to obtain a ginseng solution. Next, pectinase andbeta-galactosidase are added to the ginseng solution under conditionseffective to ferment the ginseng solution. Then, the fermented ginsengsolution is subjected to an extraction with a second solvent to obtain afermented ginseng extract. Finally, the fermented ginseng extract isconcentrated to produce a fermented ginseng concentrate.

Another aspect of the present invention relates to fermented ginsengconcentrates and fermented ginseng powder prepared by the above methods,as well as food compositions or functional food compositions containingsuch fermented ginseng concentrates and powder.

The methods for preparing a fermented ginseng concentrate and fermentedginseng powder according to the present invention involve simple stepsand are capable of producing a fermented ginseng concentrate or powderhaving a high IH-901 content. Due to their high IH-901 content, thefermented ginseng concentrate or powder prepared according to themethods of the present invention can be effectively used in functionalfood compositions.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph depicting the results from a high-pressure liquidchromatography analysis of the fermented ginseng concentrate of thepresent invention.

FIG. 2 is a graph showing the average plasma concentrations of IH-901over time for the subjects who took the fermented ginseng concentrate ofthe present invention.

FIG. 3 is a graph showing the maximum plasma concentrations (C_(max)) ofIH-901 of each subject.

FIG. 4 is a graph showing the times to reach maximum plasmaconcentration (T_(max)) of IH-901 of each subject.

FIG. 5 is a graph showing the area under the plasma concentration timecurve (AUC) of each subject.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to a method for preparing a fermentedginseng concentrate.

The method first involves subjecting ginseng to an extraction with asolvent to obtain a ginseng extract. Examples of ginseng may include,but are not limited to, ginseng tail, white ginseng, fresh ginseng,dried ginseng, red ginseng, taekuk ginseng, Korean ginseng, Chineseginseng, Japanese ginseng, Asian ginseng, American ginseng, extractsthereof, powders thereof, and mixtures thereof.

The solvent used in the extraction of ginseng may be any solvent, suchas an aqueous solvent (e.g., water), an organic solvent, or any mixturethereof, as long as it does not affect the activity of the enzymes usedin the method. In some embodiments, the organic solvent may include,without limitation, acetonitrile, dioxane, dimethyl sulfoxide, methanol,ethanol, 1-propanol, 2-propanol, and mixtures thereof.

In some embodiments, the ginseng may be subjected to an extraction withthe above solvents by using any commonly known solvent extractionmethods. In certain embodiments, an appropriate mixture of water andorganic solvents may be used for the extraction, where the organicsolvent in the mixture may increase the solubility of the ingredients inginseng that are insoluble in water and/or the intermediates producedfrom the enzymatic reactions, resulting in an overall increase in theIH-901 content in the final product, i.e., the fermented ginsengconcentrate or powder.

Next, pectinase and beta-galactosidase are added to the ginseng extractunder conditions effective to ferment the ginseng extract. In someembodiments, the ginseng extract may be diluted with a solvent beforethe pectinase and the beta-galactosidase are added. In some embodiments,the pectinase and the beta-galactosidase are added to the ginsengextract together or at the same time. In other embodiments, thepectinase and the beta-galactosidase are added to the ginseng extractseparately or at different times.

In some embodiments, the pectinase and the beta-galactosidase may beadded to the ginseng extract in a relative ratio ranging from about100:1 to about 1:100, from about 50:1 to about 1:50, from about 20:1 toabout 1:20, from about 10:1 to about 1:10, from about 5:1 to about 1:5,from about 3:1 to about 1:3, or from about 2:1 to about 1:2. In otherembodiments, the pectinase and the beta-galactosidase may be added tothe ginseng extract in a relative ratio of about 100:1, about 50:1,about 20:1, about 10:1, about 5:1, about 3:1, about 2:1, about 1:2,about 1:3, about 1:5, about 1:10, about 1:20, about 1:50, or about1:100.

In some embodiments, the total amount of the pectinase andbeta-galactosidase added to the ginseng extract may range from about0.01 wt. % to about 50 wt. %, from about 0.05 wt. % to about 50 wt. %,from about 0.1 wt. % to about 50 wt. %, from about 0.5 wt. % to about 50wt. %, from about 1 wt. % to about 50 wt. %, from about 2 wt. % to about50 wt. %, from about 5 wt. % to about 50 wt. %, from about 10 wt. % toabout 50 wt. %, from about 25 wt. % to about 50 wt. %, from about 0.01wt. % to about 0.05 wt. %, from about 0.01 wt. % to about 0.1 wt. %,from about 0.01 wt. % to about 0.5 wt. %, from about 0.01 wt. % to about1 wt. %, from about 0.01 wt. % to about 2 wt. %, from about 0.01 wt. %to about 5 wt. %, from about 0.01 wt. % to about 10 wt. %, from about0.01 wt. % to about 25 wt. %, from about 0.05 wt. % to about 0.1 wt. %,from about 0.1 wt. % to about 0.5 wt. %, from about 0.5 wt. % to about 1wt. %, from about 1 wt. % to about 2 wt. %, from about 2 wt. % to about5 wt. %, from about 5 wt. % to about 10 wt. %, or from about 10 wt. % toabout 25 wt. %, based on the total weight of the ginseng extract orginseng. In other embodiments, the total amount of the pectinase andbeta-galactosidase added to the ginseng extract may be about 0.01 wt. %,about 0.05 wt. %, about 0.1 wt. %, about 0.5 wt. %, about 1 wt. %, about2 wt. %, about 5 wt. %, about 10 wt. %, about 25 wt. %, or about 50 wt.%, based on the total weight of the ginseng extract or ginseng.

In some embodiments, the pectinase and the beta-galactosidase are addedto the ginseng extract where the reaction is carried out at a pH of fromabout 3 to about 8, from about 4 to about 8, from about 4.5 to about 8,from about 5 to about 8, from about 6 to about 8, from about 3 to about4, from about 3 to about 4.5, from about 3 to about 5, from about 3 toabout 6, from about 4 to about 4.5, from about 4.5 to about 5, or fromabout 5 to about 6. In other embodiments, the reaction is carried out ata pH of about 3, about 4, about 4.5, about 5, about 6, or about 8. Thereaction, however, may be carried out at any pH as long as theactivities of the pectinase and the beta-galactosidase are maintained.The pH may be adjusted by adding to the ginseng extract solutions, suchas but not limited to, a phosphate solution, citric acid solution, andsodium citrate buffer solution.

The reaction temperature for adding the pectinase and thebeta-galactosidase to the ginseng extract may be any temperature as longas the activities of the pectinase and beta-galactosidase aremaintained. In some embodiments, the reaction temperature range mayrange from about 10° C. to about 70° C., from about 30° C. to about 70°C., from about 40° C. to about 70° C., from about 50° C. to about 70°C., from about 60° C. to about 70° C., from about 10° C. to about 30°C., from about 10° C. to about 40° C., from about 10° C. to about 50°C., from about 10° C. to about 60° C., from about 30° C. to about 40°C., from about 40° C. to about 50° C., or from about 50° C. to about 60°C. In other embodiments, the reaction temperature may be about 10° C.,about 30° C., about 40° C., about 50° C., about 60° C., or about 70° C.

Further, the reaction time may be any length of time, as long as theactivities of the pectinase and beta-galactosidase are maintained. Insome embodiments, the reaction time may range from about 1 hour to about72 hours, from about 12 hours to about 72 hours, from about 24 hours toabout 72 hours, from about 48 hours to about 72 hours, from about 60hours to about 72 hours, from about 1 hour to about 12 hours, from about1 hour to about 24 hours, from about 1 hour to about 48 hours, fromabout 1 hour to about 60 hours, from about 12 hours to about 24 hours,from about 24 to about 48 hours, or from about 48 to about 60 hours. Inother embodiments, the reaction time may be about 1 hour, about 12hours, about 24 hours, about 48 hours, about 60 hours, or about 72hours.

Finally, the fermented ginseng extract is concentrated to produce afermented ginseng concentrate. In some embodiments, the concentrating ofthe fermented ginseng extract may involve initially carrying out acentrifugation of the fermented ginseng extract and then concentratingonly the separated supernatant. In other embodiments, the concentratingof the fermented ginseng extract may involve concentrating the fermentedginseng extract without any pre-processing steps. The fermented ginsengextract may be concentrated by using commonly used devices, such as butnot limited to, a vacuum decompression concentrator.

In some embodiments, the method of the present invention may furtherinclude drying the prepared fermented ginseng concentrate (which may bein a liquid form) to produce fermented ginseng powder. The drying may becarried out by any conventional drying method, such as but not limitedto, drying under reduced pressure, hot-air drying, spray drying,fluidized bed drying, fluidized bed granulation, and freeze drying orlyophilization.

The present invention also relates to a method for preparing a fermentedginseng concentrate. The method first involves suspending ginseng in afirst solvent to obtain a ginseng solution. Next, pectinase andbeta-galactosidase are added to the ginseng solution under conditionseffective to ferment the ginseng solution. Then, the fermented ginsengsolution is subjected to an extraction with a second solvent to obtain afermented ginseng extract. In some embodiments, the first and secondsolvents may be an aqueous solvent (e.g., water), an organic solvent, ora mixture thereof. Finally, the fermented ginseng extract isconcentrated to produce a fermented ginseng concentrate. Descriptionsregarding the various conditions used in this method, for example, withrespect to addition of the pectinase and beta-galactosidase, extraction,and concentration already described above are not necessarily repeatedherein.

Another aspect of the present invention relates to fermented ginsengconcentrates and fermented ginseng powder prepared by the above methods.The above methods of the present invention involve directly addingpectinase and beta-galactosidase to a ginseng extract or ginsengsolution under conditions effective to ferment the ginseng extract orsolution and thus are simple methods for preparing fermented ginsengconcentrates or powder having a high IH-901 content. Since the fermentedginseng concentrate and powder prepared by the above methods of thepresent invention have a high IH-901 content, they can be effectivelyused as functional food compositions.

Another aspect of the present invention relates to food compositionscontaining the above fermented ginseng concentrate or powder, as well asfunctional food compositions containing a therapeutically effectiveamount of the above fermented ginseng concentrate or powder.

The fermented ginseng concentrate and powder of the present inventionmay contain a large amount of IH-901, which is known to possessimmune-enhancing, anti-diabetic, anticancer, anti-aging, andanti-oxidation activities. A person skilled in the art can properlydetermine the amount of the fermented ginseng concentrate or powder ofthe present invention to be added, depending on the purpose for usingthe functional food composition. Generally, the fermented ginsengconcentrate or powder of the present invention may be added to thefunctional food composition in an amount ranging from about 0.1 wt % toabout 100 wt %, based on the total weight of the functional foodcomposition. In certain embodiments, such as when taking the functionalfood composition on a long term basis for health management, the amountof the fermented ginseng concentrate or powder of the present inventionadded to the functional food composition may be lower than the aboverange. Since there are no safety issues, however, the fermented ginsengconcentrate or powder of the present invention may be used in a verylarge amount.

In some embodiments, the food compositions or functional foodcompositions of the present invention may be prepared by adding thefermented ginseng concentrate or powder of the present invention ormixtures thereof without any pre-processing. In other embodiments, thefermented ginseng concentrate or powder of the present invention may beinitially processed by commonly known methods and other food componentsmay then be added. The food components that may be added to the foodcomposition or functional food composition of the present invention maydiffer depending on the type of the food composition or functional foodcomposition, and are not limited as long as they do not cause any sideeffects when mixed with the fermented ginseng concentrate or powder ofthe present invention.

The food compositions or functional food compositions of the presentinvention may be in a form suitable for oral consumption, for example,as soft or hard capsules, tablets, lozenges, dispersible powders orgranules, emulsions, suspensions, and tea bags composed of dried powdermade by commonly known methods. In some embodiments, the functional foodcomposition may be added to various foods, such as but not limited to,beverages, gum, candies, snacks, vitamin complexes, health functionalfoods, etc., to provide immune-enhancing, anti-diabetic, anti-cancer,anti-oxidation, and/or anti-aging effects.

Another aspect of the present invention relates to combinations of theinvention fermented ginseng concentrates and/or fermented ginseng powderwith other active and inactive ingredients. Examples of such active andinactive ingredients include the following, which is illustrative andnot limiting:

indole-3-carbinol

7 Keto DHEA

Acacia Catechu

ACAI

Acidophilus

Agrimony

Alfalfa

Almond Powder

Aloe Vera

Alpha Lipoic Acid

Alpha-Galactosidase

Amylase

Artichoke Leaf

Ascorbic Acid

Ashwagandha

Aspartic Acid

Astaxanthin

Astragalus

Avena Sativa

Bacopa Monnieri

Bamboo Shaving

Banaba Leaf

Baobab (Adansonia digitata)

Barberry (Berberis vulgaris)

Barley Grass

Beta Alanine

Beta Carotene

Beta Phenylalanine

Beta Phenylethylamine

Betaine HCI and HCL

Bifidobacterium

Bilberry

Biotin

Bitter Melon

Black Cohosh

Black Pepper

Black Walnut Hull

Blessed Thistle

Blueberry

Boldo

Boron (Amino Acid Complex)

Boswella extract

Bromelain

Buckthorn

Bupleurum

Burdock

Butcher's Broom

Butterbur

Butternut

Caffeine Anhydrous

Calcium Ascorbate & Carbonate

Calcium Chelate

Calcium Citrate

Calcium Gluconate

Calcium Pantothenate

Calcium Phosphate

Calcium Pyruvate

Calcium Silicate

Cardamon

Carotenoids Mixed

Cascara Sagrada

Cassia Bark & Leaf

Catalase

Cat's Claw

Catuaba

Cha' de bugre

Chamomile

Chapparal

Chia Seed

Chickory Root

Chickweed

Chinchona

Chinese Licorice

Chitosan

Chlorella

Choline Bitertrate

Chondroitin Sulfate

Chromium (Amino Acid Chelate)

Chromium (Picolinate)

Chrysanthemum

Cinnamon

Citric Acid Anhydrous

Citrus Bioflavonoids

Cleavers

CMO Cetyl myristoleate

Co-Enzymo Q-I0

Coffee Bean

Collagen

Colostrum

Coltsfoot

Copper (Amino Acid Chelate)

Cordyceps sinensis

Cramp Bark

Cranberry Extract

Cranesbill

Creatine

Cumin Seed

Cupric Oxide Anhydrous

Curcumin

Cyanocobalamin (Vitamin B12)

Damiana

Dandelion

D-Calcium Phosphate

Deer Antler

Devils Claw

DHEA

DL-Methionine

Dog Grass

Dogwood (Jamaican)

Don Quai

D-Ribose

Echinacea (purpurea, angustifolia and pallida)

Eleuthero

Enzyme blend (Amylase, Lactase, Protease,

Cellulase, Lipase)

Epimedium

Eucalyptus

Evening Primrose Oil

Evodia PE

Eyebright

False Unicorn

Fennel

Fenugreek

Feverfew Herb

Fish Collagen

Flax Seed Oil

Folic Acid

FOS Fructo-Oligosaccharide

Foti

Fucoxanthin

Fulvic Acid

GABA (Gamma amino butyric acid)

Galactoamylase

Garcina Cambogia

Gardenia

Garlic Powder

Gentian Root

Ginger Root Extract

Gingko Biloba

Glucoamylase

Glucosamine

Glucosamine Sulfate

Goat's Rue

Goji Pwd & PE

Goldenseal (Various)

Gotu Kola

Grape Seed Extract

Gravel

Graviola

Green Coffee Bean

Green Lipped Mussel

Green Tea

Guarana

Guggul

Gugulipid

Gymnema Sylvestre

Hawthorne Extract

Hemicellulase

Hesperiden

Hibiscus

Horse Chestnut

Horsetail

Hyaluronic Acid

Hyssop

Indole 3-Carbinol

Inositol

Inulin

Iodine (Potassium Iodide)

Iron (Ferrochel Amino Acid Chelate)

Iscador

Jujube

Kale

Kelp (Lamineria)

Kola Nut

Kudzu

Kyo-Dophilus

L Acidophilus

Lactobacillus

L-Alanine

L-Arginine

L-Arginine AKG

L-Aspartic Acid

Lavender

L-Carnitine

L-Carnosine

L-Citrulline

L-Cystine

Lecithin

Lemon Balm

L-Gluconate

L-Glutamic Acid

L-Glutamine

L-Glutathione

L-Glycine

L-Histidine HCL

Licorice Root

Lipoic Acid

L-Isoleucine

L-Leucine

L-Lysine

L-Methionine

L-Norvaline

Lobelia

Long Jack (Tongkat Ali)

L-Ornithine

Lovage

L-Phenylalanine

L-Proline

L-Selenomethionine

L-Serine

L-Theanine

L-Threonine

L-Tyrosine

L-Valine

Lycium

Lycopene

Lysozyme

Maca Root

Magnesium (Amino Acid Chelate)

Magnesium Carbonate

Magnesium Citrate

Magnesium Malate

Magnesium Oxide

Magnolia

Maitake Mushroom

Maltase

Manganese

Mangosteen

Mannitol

Marsh Mallow

Melatonin

Menthol Crystals USP

Microcrystalline Cellulose

Milk Thistle

Molybdenum

Motherwort

MSM (methylsulfonylmethane)

Mucuna

Mugwort

Muira Puama

Mullein

Myrrh (Guggul)

N-Acetyl L-Carnitine

N-Acetyl L-Cysteine

N-Acetyl-L-Tyrosine

Nattokinase

Natural Fish Oil

Neem Leaf

Nettle Leaf

Neutral Protease

Niacin (Niacinamide) (Vitamin B3)

Nopal Cactus

North American Ginseng

OKG (ornithine alpha-ketoglutarate

Oldenlandia

Olive Leaf

Olive Oil

Paba

Pancreatin

Pantothenic Acid

Papain

Passion Flower

Pau D′ Arco

Pectinase

Pepsin

Peptidase

Phosphatidylserine

Phosphorous (Magnesium Phosphate)

Phytase

Pine Bark (Various)

Pine Needle extract

Plantain

Pomegranate

Poria Cocos

Potassium Citrate

Potassium Iodine

Potassium (Citrate)

Pregnenolone

Prickly Ash Bark

Psyllium Husk

Pygeum Bark

Pyridoxine hydrochloride (Vitamin B6)

Queen of the Meadow

Quercetin

Red Tea Powder

Red Clover

Resveratrol

Rhodiola

Rhubarb

Riboflavin (Vitamin B2)

RNA

Rose Hip

Rosemary

Royal Jelly

Rutin

Sarsparilla

Saussurea Root

Saw Palmetto

Schizandra

Scutellaria baicalensis

Scutellaria Root

Selenium

Self Heal

Senna

Serratiopeptidase

Shark Cartilage

Sheep Sorrel

Shilatjit

Silymarin

Skullcap

Slippery Elm Bark

SOD Superoxide dismutase

Sodium Ascorbate

Sodium Saccharine

Spirulina

Squawvine

St. Johns Wort

Stone Root

Sucrase

Suma

Thiamin (Vitamin BI)

Thioproline

Tocopherols Mixed (alpba, beta, and gamma)

Tribulus (Various)

Triphala

Trypsin

Turmeric

Undaria Pinnatifida

Uva Ursi

Valerian Root

Vitamin A

Vitamin B1

Vitamin B-12

Vitamin B2

Vitamin B3 (Niacinamide)

Vitamin B6

Vitamin C

Vitamin D (Cholecalciferol)

Vitamin D2

Vitamin D3

Vitamin E (Natural-Succinate)

Vitamin K1 (Phytonadione)

White Kidney Bean

White Willow

Witch Hazel

Wormwood

Xylanase

Xylitol

Yarrow

Yellow Dock

Yerba Mate

Yohimbe

Yucca (all species)

Zeaxanthin

Zinc

Zinc Oxide

These combinations of the invention fermented ginseng concentratesand/or fermented ginseng powder with other active and inactiveingredients such as those listed above include the invention fermentedginseng concentrates and/or fermented ginseng powder in any amount andone or more other active and/or inactive ingredients in any amount. Suchcombinations may be in solid, liquid, powder, gel, etc. form, and may bepresent alone or in foodstuffs, drinks, tablets, pills, capsules, etc.Example amounts of the invention fermented ginseng concentrates and/orfermented ginseng powder include 0.01-99.99 wt. % based on total weightof the combination, including for example 0.1, 1, 3, 5, 10, 15, 20, 30,40, 50, 60, 70, 80, 90, 95, etc. wt. %, and example amounts of the otheractive and/or inactive ingredients include 0.01-99.99 wt. % based ontotal weight of the combination, including for example 0.1, 1, 3, 5, 10,15, 20, 30, 40, 50, 60, 70, 80, 90, 95, etc. wt. %. Example amounts ofthe combination present in other compositions such as foodstuffs,drinks, tablets, pills, capsules, etc. is 0.1-99.9 wt. % based on totalweight of the composition. Preferred combination amounts are thoseamounts of the invention fermented ginseng concentrates and/or fermentedginseng powder that provide a synergistic increase in the effect of theone or more other active and/or inactive ingredients, such combinationsbeing referred to herein as synergistic combinations. Preferredcombinations of the invention fermented ginseng concentrates and/orfermented ginseng powder with other active and inactive ingredientsinclude the following, which again is illustrative and not limiting:

Acacia Catechu

Aloe Vera

Alpha Lipoic Acid

Ashwagandha

Banaba Leaf

Clovers

Cinnamon

Co-Enzymo Q-I0

cordyceps sinensis

Curcumin

DHEA

Ginkgo biloba

Guarana

Lycopene

NAC N-Acetyl-L-Cysteine

OKG (ornithine alpha-ketoglutarate)

Quercitin

Resveratrol

Rhodiola

Saw Palmetto

Scutellaria baicalensis

Vanadium

Another aspect of the present invention relates to novel uses of theinvention fermented ginseng concentrates and/or fermented ginsengpowder, and to novel uses of the invention combinations of the inventionfermented ginseng concentrates and/or fermented ginseng powder withother active and inactive ingredients. These uses include those usesknown for the above-listed other active and/or inactive ingredients.

EXAMPLES

The following examples are provided to illustrate embodiments of thepresent invention but are by no means intended to limit its scope.

Example 1 Preparation of Fermented Ginseng Concentrate Using Pectinaseand Beta-Galactosidase

<1-1> Preparation of Fermented Ginseng Concentrate Using Ginseng Tailand White Ginseng

5 g of ginseng tail and 5 g of white ginseng were extracted with amixture of water and ethanol (mixing ratio of 1:1; in an amountcorresponding to 500% compared to the raw materials) four times at 80°C. at 3-hour intervals to obtain 7 g of ginseng extract. 100 ml of waterand then 0.3 g of pectinase and 1 g of beta-galactosidase were added tothe ginseng extract, where the reaction mixture was maintained at 50°C., pH 4-5, for 48 hours. The reactant was filtered and concentratedunder reduced pressure at 80° C. to give 6.3 g of fermented ginsengconcentrate according to the present invention.

<1-2> Preparation of Fermented Ginseng Concentrate Using Ginseng Tailand White Ginseng

7 g of ginseng extract was prepared as described in Example <1-1> above.100 ml of water and then 1 g of beta-galactosidase were added to theginseng extract, where the reaction mixture was maintained at 50° C. for24 hours, and then the enzyme was inactivated by subjecting the mixtureat a temperature of 80° C. for 3 hours. The reactant was cooled and thepH was adjusted to 4-5 with citric acid. Then, 0.3 g of pectinase wasadded thereto where the mixture was subjected to a reaction for 24hours. Subsequently, the reaction mixture was filtered and concentratedunder reduced pressure at 80° C. to give 5.9 g of fermented ginsengconcentrate according to the present invention.

<1-3> Preparation of Fermented Ginseng Concentrate Using Ginseng Tailand White Ginseng

5 g of ginseng tail and 5 g of white ginseng were extracted with amixture of water and ethanol (mixing ratio of 1:1; in an amountcorresponding to 500% compared to the raw materials) to obtain 7 g ofginseng extract. 100 ml of water and then 0.5 g of pectinase and 0.7 gof beta-galactosidase were added to the ginseng extract, where thereaction mixture was maintained at 50° C., pH 4-5, for 48 hours. Thereactant was filtered and concentrated under reduced pressure at 80° C.to give 6.2 g of fermented ginseng concentrate according to the presentinvention.

<1-4> Preparation of Fermented Ginseng Concentrate Using Ginseng Tailand White Ginseng

5 g of ginseng tail and 5 g of white ginseng were extracted with amixture of water and ethanol (mixing ratio of 1:1; in an amountcorresponding to 500% compared to the raw materials) to obtain 7 g ofginseng extract. 100 ml of water and then 0.9 g of pectinase and 0.6 gof beta-galactosidase were added to the ginseng extract, where thereaction mixture was maintained at 50° C., pH 4-5, for 48 hours. Thereactant was filtered and concentrated under reduced pressure at 80° C.to give 5.9 g of fermented ginseng concentrate according to the presentinvention.

<1-5> Preparation of Fermented Ginseng Concentrate Using Ginseng Tailand White Ginseng

5 g of ginseng tail and 5 g of white ginseng were extracted with amixture of water and ethanol (mixing ratio of 1:1; in an amountcorresponding to 500% compared to the raw materials) to obtain 7 g ofginseng extract. 100 ml of water and then 1.2 g of pectinase and 0.2 gof beta-galactosidase were added to the ginseng extract, where thereaction mixture was maintained at 50° C., pH 4-5, for 48 hours. Thereactant was filtered and concentrated under reduced pressure at 80° C.to give 6.3 g of fermented ginseng concentrate according to the presentinvention.

<1-6> Preparation of Fermented Ginseng Concentrate Using Ginseng Tail

10 g of ginseng tail was extracted with 100 ml of water to obtain 7 g ofginseng extract. The pH of the extract was adjusted to 3-4 with citricacid. 0.3 g of pectinase and 1 g of beta-galactosidase were added to theginseng extract, where the mixture was subjected to a reaction at 50° C.for 48 hours. Subsequently, the reactant was filtered and concentratedby the same method as described in Example <1-1> above to obtain 6.5 gof fermented ginseng concentrate (I) according to the present invention.

Alternatively, 10 g of ginseng tail was extracted with a mixture ofwater and ethanol by the same method as described in Example <1-1> aboveto obtain 7.2 g of ginseng extract. The pH of the extract was adjustedto 3-4 with citric acid. 0.3 g of pectinase and 1 g ofbeta-galactosidase were added to the ginseng extract, where the mixturewas filtered and concentrated by the same method as described in Example<1-1> above to obtain 6.8 g of fermented ginseng concentrate (II)according to the present invention.

<1-7> Preparation of Fermented Ginseng Concentrate Using Ginseng Tail

10 g of ginseng tail was extracted with 100 ml of water to obtain 7 g ofginseng extract. 100 ml of water and then 1 g of beta-galactosidase wereadded to the ginseng extract where the reaction mixture was maintainedat 50° C. for 24 hours, and then the enzyme was inactivated bysubjecting the mixture at a temperature of 80° C. for 3 hours. Thereactant was cooled and the pH was adjusted to 4-5 with citric acid.Then, 0.3 g of pectinase was added thereto and reacted at 50° C. for 24hours. Subsequently, the reactant was filtered and concentrated underreduced pressure at 80° C. to obtain 6.5 g of fermented ginsengconcentrate according to the present invention.

<1-8> Preparation of Fermented Ginseng Concentrate Using White Ginseng

1 kg of white ginseng was extracted with 5% of ethanol to obtain 540 gof ginseng extract. 7 g of the extract was concentrated and thensuspended in water. 0.3 g of pectinase and 1 g of beta-galactosidasewere added thereto, where the mixture was reacted, filtered, andconcentrated by the same method as described in Example <1-1> above toobtain 5.2 g of fermented ginseng concentrate according to the presentinvention.

<1-9> Preparation of Fermented Ginseng Concentrate Using White Ginseng 1kg of white ginseng was extracted with 5 l of ethanol to obtain 540 g ofginseng extract. 7 g of the extract was concentrated and then suspendedin water. 0.5 g of pectinase and 0.5 g of beta-galactosidase were addedthereto, where the mixture was reacted, filtered, and concentrated bythe same method as described in Example <1-1> above to obtain 5.1 g offermented ginseng concentrate according to the present invention.

<1-10> Preparation of Fermented Ginseng Concentrate Using White Ginseng

1 kg of white ginseng was extracted with 5 l of ethanol to obtain 540 gof ginseng extract. 7 g of the extract was concentrated and thensuspended in water. 1.5 g of pectinase and 0.2 g of beta-galactosidasewere added thereto, where the mixture was reacted, filtered, andconcentrated by the same method as described in Example <1-1> above toobtain 6.2 g of fermented ginseng concentrate according to the presentinvention.

<1-11> Preparation of Fermented Ginseng Concentrate Using Fresh Ginseng

6 g of fresh ginseng was sliced into pieces and sterilized. After theginseng pieces were suspended in water, the pH was adjusted to 3-4.5with citric acid, and 0.3 g of pectinase and 1 g of beta-galactosidasewere added thereto where the mixture was subjected to a reaction at 50°C. for 72 hours. The reactant was extracted with a mixture of water andethanol prepared by the same method as described in Example <1-1> abovefour times at 80° C. for 4 hours. Then, the extract was filtered andconcentrated to obtain 3.5 g of fermented ginseng concentrate accordingto the present invention.

<1-12> Preparation of Fermented Ginseng Concentrate Using Fresh Ginseng

6 g of fresh ginseng was sliced into pieces and sterilized. After theginseng pieces were suspended in water, 1 g of beta-galactosidase wasadded thereto where the mixture was subjected to a reaction at 50° C.for 24 hours and inactivated at 80° C. for 3 hours. The reactant wascooled and the pH was adjusted to 4-5 with citric acid. Then, 0.3 g ofpectinase was added thereto and reacted at 50° C. for 24 hours.Subsequently, the reactant was filtered and then extracted with amixture of water and ethanol prepared by the same method as described inExample <1-1> above four times at 80° C. for 4 hours. Then, the extractwas concentrated under reduced pressure at 80° C. to obtain 2.9 g offermented ginseng concentrate according to the present invention.

<1-13> Preparation of Fermented Ginseng Concentrate Using Fresh Ginseng

6 g of fresh ginseng was sliced into pieces and sterilized. After theginseng pieces were suspended in water, the pH was adjusted to 3-4 withcitric acid. Then, 0.7 g of pectinase and 0.6 g of beta-galactosidasewere added thereto where the mixture was subjected to a reaction at 50°C. for 72 hours. Subsequently, the reactant was filtered andconcentrated to obtain 2.9 g of fermented ginseng concentrate accordingto the present invention.

<1-14> Preparation of Fermented Ginseng Concentrate Using Fresh Ginseng

6 g of fresh ginseng was sliced into pieces and sterilized. After theginseng pieces were suspended in water, 0.7 g of beta-galactosidase wasadded thereto where the mixture was subjected to a reaction at 50° C.for 24 hours and inactivated at 80° C. for 3 hours. The reactant wascooled and the pH was adjusted to 4-5 with citric acid. Then, 0.6 g ofpectinase was added thereto and reacted at 50° C. for 24 hours.Subsequently, the reactant was filtered and then extracted with amixture of water and ethanol prepared by the same method as described inExample <1-1> above four times at 80° C. for 4 hours. Then, the extractwas concentrated under reduced pressure at 80° C. to obtain 2.3 g offermented ginseng concentrate according to the present invention.

<1-15> Preparation of Fermented Ginseng Concentrate Using Fresh Ginseng

6 g of fresh ginseng was sliced into pieces and sterilized. After theginseng pieces were suspended in water, the pH was adjusted to 3-4.5with citric acid. Then, 0.9 g of pectinase and 0.5 g ofbeta-galactosidase were added thereto where the mixture was subjected toa reaction at 50° C. for 72 hours. Subsequently, the reactant wasfiltered and concentrated to obtain 2.5 g of fermented ginsengconcentrate according to the present invention.

<1-16> Preparation of Fermented Ginseng Concentrate Using Fresh Ginseng

6 g of fresh ginseng was sliced into pieces and sterilized. After theginseng pieces were suspended in water, the pH was adjusted to 3-4.5with citric acid. Then, 2 g of pectinase and 0.2 g of beta-galactosidasewere added thereto where the mixture was subjected to a reaction at 50°C. for 72 hours. Subsequently, the reactant was filtered andconcentrated to obtain 3.3 g of fermented ginseng concentrate accordingto the present invention.

<1-17> Preparation of Fermented Ginseng Concentrate Using Fresh Ginseng

6 g of fresh ginseng was sliced into pieces and sterilized. After theginseng pieces were suspended in water, 0.5 g of beta-galactosidase wasadded thereto where the mixture was subjected to a reaction at 50° C.for 24 hours and inactivated at 80° C. for 3 hours. The reactant wascooled and the pH was adjusted to 4-5 with citric acid. Then, 1.5 g ofpectinase was added thereto and reacted at 50° C. for 24 hours.Subsequently, the reactant was filtered and then extracted with amixture of water and ethanol prepared by the same method as described inExample <1-1> above four times at 80° C. for 4 hours. Then, the extractwas concentrated under reduced pressure at 80° C. to obtain 3.1 g offermented ginseng concentrate according to the present invention.

<1-18> Preparation of Fermented Ginseng Concentrate Using Ginseng Powder

7 g of ginseng powder was suspended in water. The pH was adjusted to3-4.5 with citric acid. The suspended ginseng powder was reacted with0.3 g of pectinase and 1 g of beta-galactosidase and extracted by thesame method as described in Example <1-11> above, and then filtered andconcentrated to obtain 3.7 g of fermented ginseng concentrate accordingto the present invention.

Comparative Example 1 Preparation of Fermented Ginseng Concentrate UsingPectinase Only

100 ml of water was added to 7 g of ginseng extract prepared by the samemethod as described in Example <1-1> above. Then, 1.3 g of pectinase wasadded to the extract, which was subsequently reacted and concentratedunder reduced pressure by the same method as described in Example <1-1>above to obtain 5.6 g of fermented ginseng concentrate according to thepresent invention.

Comparative Example 2 Preparation of Fermented Ginseng Concentrate UsingBeta-Galactosidase Only

100 ml of water was added to 7 g of ginseng extract prepared by the samemethod as described in Example <1-1> above. Then, 1.3 g ofbeta-galactosidase was added to the extract, which was subsequentlyreacted and concentrated under reduced pressure by the same method asdescribed in Example <1-1> above to obtain 5.4 g of fermented ginsengconcentrate according to the present invention.

Experimental Example 1 The IH-901 Content in the Fermented GinsengConcentrate of the Present Invention

In order to analyze the content of IH-901(20-0-β-D-glucopyranosyl-20(S)-protopanaxadiol) in the fermented ginsengconcentrate prepared by the method described in Example <1-1> above, 1 gof the obtained fermented ginseng concentrate was taken and extractedwith 60 ml of water-saturated butanol four times. The butanol fractionwas concentrated to obtain 120 mg of concentrate, and the concentratewas dissolved in methanol to analyze the IH-901 content by ultraperformance liquid chromatography (UPLC). The results of the UPLCanalysis are shown in FIG. 1. The IH-901 content in the ginseng extractprepared in Example <1-1> above was also measured in the same manner asabove.

Further, the IH-901 content in the fermented ginseng concentrateprepared by the method described in Comparative Example 1 or ComparativeExample 2 above was analyzed in the same manner as above.

The results of the above analyses are summarized in Table 1 below.

TABLE 1 Content of each component Fermented Fermented Fermented GinsengGinseng Ginseng Ginseng Extract of Concentrate Concentrate ConcentrateExample of Example of Comp. of Comp. Component 1-1 1-1 Example 1 Example2 Ginsenoside 17.6 mg/g 1.2 mg/g 6.3 mg/g 3.2 mg/g Rb1 Ginsenoside 14.6mg/g 1.1 mg/g 7.1 mg/g 5.7 mg/g Rb2 Ginsenoside 18.9 mg/g 0.1 mg/g 9.3mg/g 6.3 mg/g Rc Ginsenoside  7.9 mg/g 1.4 mg/g 2.2 mg/g 4.2 mg/g RdIH-901    0 mg/g  36 mg/g  24 mg/g  10 mg/g

As shown in Table 1 above, the fermented ginseng concentrate accordingto the present invention, in contrast to the ginseng extract, contains alarge amount of IH-901. Furthermore, the IH-901 content in the fermentedginseng concentrate according to the present invention is 3.6 timeshigher than that in the fermented ginseng concentrate prepared usingbeta-galactosidase only and 1.5 times higher than that in the fermentedginseng concentrate prepared using pectinase only.

Experimental Example 2 Study on Body's Absorption of IH-901 of theFermented Ginseng Concentrate of the Present Invention

Twenty four healthy male volunteers of ages ranging from 20 to 45, whosebody weights are within 20% of the ideal body weights, were used assubjects for the study (randomized, 2×2 cross-over design).

Each volunteer received the fermented ginseng extract or ginseng extractfor pharmacokinetic characteristic assessments. Blood samples were takenat 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 hours afteradministration of the fermented ginseng extract or ginseng extract andwere analyzed by LC-MS/MS. The average plasma concentrations of IH-901over time are shown in FIG. 2. The average maximum plasma concentration(C_(max)), average time to reach maximum plasma concentration (T_(max)),and area under the plasma concentration time curve (AUC) values measuredare shown in Table 2 below, where C_(max) is the average of the maximumconcentration values of each subject irrespective of time and T_(max) isthe average of the time values corresponding to the C_(max) values ofeach subject. The C_(max), T_(max), and AUC values for each subject areshown in FIGS. 3 to 5.

TABLE 2 C_(max) T_(max) AUC Fermented 325.00 ± 91.97  3.29 2083.09 ±524.68  ginseng concentrate ng/ml hr ng/ml Ginseng 13.88 ± 7.24 12.04134.5 ± 63.10 concentrate ng/ml hr ng/ml

As shown in Table 2 above, the C_(max), AUC, and T_(max) of IH-901 inthe fermented ginseng concentrate are about 24 times higher, 15 timeshigher, and 3.7 times lower than those of the ginseng concentrate,respectively.

Therefore, it was found that when a ginseng concentrate was taken, eachindividual had different capabilities with respect to metabolizingginsenosides to IH-901 and only a small amount of IH-901 was absorbed inthe body. Further, when a ginseng concentrate was taken, each individualexhibited different average times in reaching the maximum plasmaconcentration.

In contrast, when a fermented ginseng concentrate was taken, the amountof IH-901 absorbed and the average time to reach maximum plasma levelwere constant for each individual. Further, when a fermented ginsengconcentrate was taken, a large amount of IH-901 was absorbed in thebody.

Accordingly, the above results demonstrate that a steady and constanteffect (with little individual variation) can be expected when subjectstake fermented ginseng concentrate.

Example 2 Preparation of Fermented Ginseng Powder According to thePresent Invention <2-1> Preparation of Fermented Ginseng Powder UsingGinseng Tail and White Ginseng

100 g of water was added to 7 g of an extract of ginseng prepared by thesame method as described in Example <1-1> above. Then, 0.3 g ofpectinase and 1 g of beta-galactosidase were added to the extract, whichwas subsequently reacted at 50° C., pH 4-5, for 24 hours. The reactedextract was dried under reduced pressure at 80° C. to obtain 4.23 g offermented ginseng powder according to the present invention.

<2-2> Preparation of Fermented Ginseng Powder Using Ginseng Powder

7 g of ginseng powder was suspended in water, and then the pH wasadjusted to 3-4.5. Next, 0.3 g of pectinase and 1 g ofbeta-galactosidase were added to the suspension, which was subsequentlyreacted at 50° C. for 24 hours and extracted with a mixture of water andethanol prepared by the same method as in described in Example <1-1>above four times at 80° C. for 4 hours. The extract was then dried underreduced pressure to obtain 2.6 g of fermented ginseng powder.

Although the invention has been described in detail for the purpose ofillustration, it is understood that such detail is solely for thatpurpose, and variations can be made therein by those skilled in the artwithout departing from the spirit and scope of the invention which isdefined by the following claims.

The above written description of the invention provides a manner andprocess of making and using it such that any person skilled in this artis enabled to make and use the same, this enablement being provided inparticular for the subject matter of the appended claims, which make upa part of the original description.

As used herein, the words “a” and “an” and the like carry the meaning of“one or more.”

The phrases “selected from the group consisting of,” “chosen from,” andthe like include mixtures of the specified materials. Terms such as“contain(s)” and the like are open terms meaning ‘including at least’unless otherwise specifically noted.

All references, patents, applications, tests, standards, documents,publications, brochures, texts, articles, etc. mentioned herein areincorporated herein by reference. Where a numerical limit or range isstated, the endpoints are included. Also, all values and subrangeswithin a numerical limit or range are specifically included as ifexplicitly written out.

The above description is presented to enable a person skilled in the artto make and use the invention, and is provided in the context of aparticular application and its requirements. Various modifications tothe preferred embodiments will be readily apparent to those skilled inthe art, and the generic principles defined herein may be applied toother embodiments and applications without departing from the spirit andscope of the invention. Thus, this invention is not intended to belimited to the embodiments shown, but is to be accorded the widest scopeconsistent with the principles and features disclosed herein. In thisregard, certain embodiments within the invention may not show everybenefit of the invention, considered broadly.

What is claimed is:
 1. A combination comprising a fermented ginsengconcentrate and at least one other active or inactive ingredient,wherein the fermented ginseng concentrate is prepared by a methodcomprising: subjecting ginseng to an extraction with a solvent to obtaina ginseng extract; adding pectinase and beta-galactosidase to theginseng extract under conditions effective to ferment the ginsengextract; and concentrating the fermented ginseng extract to produce afermented ginseng concentrate.
 2. The combination according to claim 1,wherein the ginseng is one or more of ginseng tail, white ginseng, freshginseng, dried ginseng, red ginseng, taekuk ginseng, Korean ginseng,Chinese ginseng, Japanese ginseng, Asian ginseng, American ginseng,extracts thereof, powders thereof, and mixtures thereof, and the atleast one other active or inactive ingredient is selected from the groupconsisting of: Acacia Catechu Aloe Vera Alpha Lipoic Acid AshwagandhaBANABA LEAF BLUEBERRY Cinnamon Cur cumin Clovers Co-Enzymo Q-I0cordyceps sinensis DHEA Ginkgo biloba Guarana Lycopene NACN-Acetyl-L-Cysteine OKG (ornithine alpha-ketoglutarate) QuercitinResveratrol Rhodiola Saw Palmetto Scutellaria baicalensis and Vanadium.3. The combination according to claim 1, wherein the combination is asynergistic combination.
 4. The combination according to claim 2,wherein the combination is a synergistic combination.
 5. A combinationcomprising a fermented ginseng concentrate and at least one other activeor inactive ingredient, wherein the fermented ginseng concentrate isprepared by a method comprising: suspending ginseng in a first solventto obtain a ginseng solution; adding pectinase and beta-galactosidase tothe ginseng solution under conditions effective to ferment the ginsengsolution; subjecting the fermented ginseng solution to an extractionwith a second solvent to obtain a fermented ginseng extract; andconcentrating the fermented ginseng extract to produce a fermentedginseng concentrate.
 6. The combination according to claim 5, whereinthe ginseng is one or more of ginseng tail, white ginseng, freshginseng, dried ginseng, red ginseng, taekuk ginseng, Korean ginseng,Chinese ginseng, Japanese ginseng, Asian ginseng, American ginseng,extracts thereof, powders thereof, and mixtures thereof, and the atleast one other active or inactive ingredient is selected from the groupconsisting of: Aloe Vera Alpha Lipoic Acid Ascorbic Acid Aspartic AcidCaffeine Calcium Carabonate Flax Seed Oil Folic Acid Ginger Root ExtractGinkgo biloba Extract Glucosamine Sulfate Quercetin Beta Carotene FolicAcid L-Cystine Lecithin St. Johns Wort, and Zinc Oxide.
 7. Thecombination according to claim 5, wherein the combination is asynergistic combination.
 8. The combination according to claim 6,wherein the combination is a synergistic combination.